Skin conditioner

ABSTRACT

Moisture retention ability of skin is improved and/or skin is protected or treated for another purpose by applying thereto a composition containing at least one of the following compounds: ethanolamine, 2-methoxyethylamine, O-phosphorylethanolamine, 2-ethylaminoethanol, diethanolamine, 2-dimethylaminoethanol, choline, 2-amino-2-hydroxymethyl-1,3-propanediol, noradrenalin, phenethylamine, ethylenediamine, taurine, phosphatidylethanolamine, N-(2-hydroxyethyl)acetoamide, 2-(methylamino)ethanol, 2-anilinoethanol, 2-(benzylamino)ethanol, 3-amino-1-propanol, 2-amino-1-butanol, putrescine, DL-pyroglutamic acid and triethanolamine.

TECHNICAL FIELD

[0001] The present invention relates to a skin conditioner that can beused in a broad range of fields including cosmetics, quasi-drugs andpharmaceuticals.

BACKGROUND ART

[0002] In addition to that resulting from aging, human skin and scalphave recently become constantly exposed to risks from external factorssuch as ultraviolet rays, drying, air-conditioning, air pollution, otherirritants and microorganisms, and from internal factors such ascontamination by food, water or agricultural chemicals and additivesthrough them, as well as sleep, fatigue and stress.

[0003] As a result of these risks, there are many persons with unhealthyskin or persons having skin that at first appears healthy, but isactually in a functionally or structurally unhealthy state. Even personsof an age who ought to inherently have healthy skin have skin thatrequires the use of cosmetics. However, typical moisture retentionagents and oils used in current cosmetics are known to only reach thesurface of the skin, and only function as a moisture covering or oilcovering without actually acting on the skin.

[0004] On the other hand, although oils such as Vaseline have long beenused for treatment of symptoms and diseases caused by drying of theskin, these are also merely carried on the surface of the skin, therebyforcing the affected person to wait for the symptoms or disease to healnaturally. In addition, since the effects of typical drugs only act onthe particular symptom and do not promote the health of the skin itself,in environments like those found at present, if confronted with the samecause after use is discontinued, there are many cases in which thesymptom or disease recurs. In addition, drugs also constantly presentthe risk of being accompanied by adverse side effects.

DISCLOSURE OF THE INVENTION

[0005] Currently in the field of dermatology, it has become anestablished theory around the world that the corneal layer of theepidermis (stratum corneum epidermidis) is responsible for the barriermechanism that protects the body from the outside world. Therefore, wefelt that restoring the skin to its inherently healthy state is thebasis of beauty as well as the basic measure for protecting the bodyfrom all types of diseases of the skin. In order to accomplish this, theobject of the present invention is to condition the corneal layer,condition the entire epidermis and finally condition all skin tissueincluding the dermis.

[0006] In order to accomplish the above object of the present invention,the invention of claim 1 provides a skin conditioner containing one kindor two or more kinds of a compound represented by the following generalformula (1):

[0007] (wherein, R₁ represents a hydroxyl group, a lower alkoxy groupthat may optionally have a substituent, a phosphoryloxy group, an arylgroup, an amino group, a sulfonic acid group, a phosphatidyloxy group, alower alkyl group substituted with a hydroxyl group or an amino group ora lower alkyl group substituted with a guanidino group;

[0008] R₂, R₃, R₄ and R₅ each independently represent a hydrogen atom, alower alkyl group that may optionally be substituted with a hydroxylgroup, an aryl group that may optionally be substituted with a hydroxylgroup, a carboxyl group, or R₄ and R₅, together with an adjacent carbonatom, form a carbonyl group;

[0009] R₆ and R₇ each independently represent a hydrogen atom, a loweralkyl group that may optionally be substituted with a hydroxyl group, alower alkylcarbonyl group, an aryl group, an aralkyl group, or R₆ and R₂represent alkylene groups, which may optionally have a substituent, thattogether form a 5-membered ring with an adjacent atom; and, nitrogenatoms in the formula may be in a quaternary form with a lower alkylgroup).

[0010] Lower alkyl groups in the present invention are straight orbranched alkyl groups having 1 to 10 carbon atoms, and preferably 1 to 5carbon atoms, examples of which include a methyl group and an ethylgroup. Lower alkoxy groups are those which are derived from theabove-mentioned lower alkyl groups, examples of which include a methoxygroup and ethoxy group. Aryl groups having 6 to 18 carbon atoms, andpreferably 6 to 10 carbon atoms, examples of which include a phenylgroup and a naphthyl group. Aralkyl groups are those in which an arylgroup is substituted for the above-mentioned lower alkyl group, examplesof which include a benzyl group and phenythyl group.

[0011] In addition, these groups may optionally be substituted with asubstituent, while preferable examples of substituent include a hydroxylgroup, amino group and carboxyl group.

[0012] The invention of claim 2 provides a skin conditioner wherein thecompound represented by general formula (1) is L-arginine.

[0013] The invention of claim 3 provides a skin conditioner wherein thecompound represented by general formula (1) is ethanolamine.

[0014] The invention of claim 4 provides a skin conditioner wherein thecompound represented by general formula (1) is a compound selected fromthe group consisting of 2-methoxyethylamine, O-phosphorylethanolamine,2-ethylaminoethanol, diethanolamine, 2-dimethylaminoethanol, choline,2-amino-2-hydroxymethyl-1,3-propanediol, noradrenalin, phenethylamine,ethylenediamine, taurine, phosphatidylethanolamine,N-(2-hydroxyethyl)acetamide, 2-(methylamino)ethanol, 2-anilinoethanol,2-(benzylamino)ethanol, 3-amino-1-propanol, 2-amino-1-butanol,putrescine, DL-pyroglutamic acid and triethanolamine.

BRIEF DESCRIPTION OF THE DRAWINGS

[0015]FIG. 1 shows the results of performing a collagen productionrecovery test on damaged fibroblasts for Examples of the presentinvention.

[0016]FIG. 2 shows the results of a moisture retention duration test onExamples of the present invention.

[0017]FIG. 3 shows the results of a moisture retention duration test onan Example of the present invention.

[0018]FIG. 4 shows the results of performing a moisture retentionability test on Examples of the present invention.

[0019]FIG. 5 shows the results of performing a moisture retentionability test on Examples of the present invention.

[0020]FIG. 6 shows the results of a 2-hour moisture retention durationtest according to Examples of the present invention.

[0021]FIG. 7 shows the results of a 2-hour moisture retention durationtest according to Examples of the present invention.

[0022]FIG. 8 shows the results of a chapped skin recovery test accordingto Examples of the present invention.

[0023]FIG. 9 shows the overall improvement (usefulness) of usingExamples of the present invention in dry eczema, xeroderma and facialdry eczema patients.

[0024]FIG. 10 shows improvement of itchiness, sclerosis andcornification by Examples of the present invention.

[0025]FIG. 11 shows improvement of scaling and cracking by Examples ofthe present invention.

[0026]FIG. 12 shows improvement of erythema, dryness and wrinkles byExamples of the present invention.

[0027]FIG. 13 shows overall improvement (usefulness) of using Examplesof the present invention in asteatosis, xeroderma, facial dry eczema andprogressive volar keratoderma (keratodermia tylodes palmarisprogressive) patients.

[0028]FIG. 14 shows improvement of itchiness, sclerosis andcornification by Examples of the present invention.

[0029]FIG. 15 shows improvement of scaling and cracking by Examples ofthe present invention.

[0030]FIG. 16 shows improvement of erythema, dryness and wrinkles byExamples of the present invention.

[0031]FIG. 17 shows changes in the severity score of vasodilation byExamples of the present invention.

[0032]FIG. 18 shows changes in the severity score of cellularinfiltration by Examples of the present invention.

[0033]FIG. 19 shows changes in the severity score of keratin hyperplasiaby Examples of the present invention.

[0034]FIG. 20 shows changes in the severity score of parakeratosis byExamples of the present invention.

[0035] FIGS. 21 to 31 show the results of a moisture retention durationtest performed on atopic skin according to Examples of the presentinvention.

[0036] FIGS. 32 to 34 show the results of a moisture retention abilitytest performed on atopic skin according to Examples of the presentinvention.

[0037] FIGS. 35 to 37 show the results of a test of transepidermalmoisture evaporation volume performed on atopic skin according toExamples of the present invention.

[0038]FIG. 38 shows the results of an allergic reaction inhibition testaccording to Examples of the present invention.

[0039] FIGS. 39 to 50 show changes in the severity score performed onatopic skin according to Examples. of the present invention.

BEST MODE FOR CARRYING OUT THE INVENTION TEST EXAMPLE 1

[0040] A collagen production recovery test was conducted on damagedfibroblasts.

[0041] Fibroblasts are cells that compose the dermis which is on theinside of the skin epidermis. Collagen produced by fibroblasts accountsfor approximately 70% of the weight of the dermis, and gives the skintightness, elasticity and flexibility. In addition, when the skinbecomes injured and so forth, it also fulfills the role of theregenerative function of the skin. As the skin ages, the amount ofcollagen decreases dramatically. Consequently, the skin loses itstightness and elasticity, and wounds are known to heal more slowly. Inaddition, even in the absence of aging of the skin, the ability toproduce collagen decreases due to various causes such as routineexposure to ultraviolet rays and radiation, and the generation of activeoxygen.

[0042] Samples:

[0043] Example 1

[0044] 1% aqueous solution of L-arginine (Nakarai Tesuku)

[0045] Example 2

[0046] 1% aqueous solution of ethanolamine (Nakarai Tesuku)

[0047] Example 3

[0048] After crushing 1 kg of rice with a crusher, 250 g of water weremixed in well while spraying followed by allowing to stand for 30minutes. Next, the rice was boiled for 60 minutes followed by theaddition of 2000 mL of water. Moreover, after adding 7.5 g each ofα-amylase and β-amylase, the mixture was allowed to stand for 10 hoursat 55° C. Next, after gradually raising the temperature and boiling for5 minutes, the mixture was cooled to 50° C. followed by the addition of30 g of citric acid, 8 g of acidic protease and 8 g of acidiccarboxypeptidase and allowing to react for 24 hours. After completion ofthe reaction, the mixture was cooled to 20° C. followed by the additionof 200 g of malted rice (Aspergillus oryzae) and pre-culturedSaccharomyces cereviciae culture broth, and fermenting at 20-25° C. for20 days.

[0049] Following completion of fermentation, the mixture waspress-filtered to obtain 2700 mL of filtrate. Next, 500 mL of activatedcharcoal were packed into a column and the filtrate was passed throughthe column. The resulting effluent was collected to obtain 2700 mL ofproduct containing 1934 mg/L of L-arginine and 162 mg/L of ethanolamine.(The concentration of L-arginine was approximately 0.2%, and that ofethanolamine was approximately 0.02%.)

[0050] Mixture of samples of Example 1 and Example 2:

[0051] Mixture of samples of Example 1 and 2 with the product of Example3:

[0052] Test Method:

[0053] Six to eight subcultures of normal human skin fibroblasts(Physicochemical Research Institute, Cell Development Bank NBIRGB) wereused in the test.

[0054] Hypoxanthine at a final concentration of 50 μM and 34.5 mU/dishof xanthine oxidase were added to the culture broth to generate activeoxygen and lower the collagen production ability of the cells.

[0055] Measurement of collagen production ability of a confluent in thesteady state was performed according to the method of Webster et al.based on the uptake of ³H-proline into the produced collagen.Furthermore, the samples were mixed with the cells to a finalconcentration of 3.3% (taking 1% to be 100% for a 1% aqueous solution)and after incubating at 37° C. for 24 hours and 5% CO₂, the ³H activitytaken up into the collagen in the cells was measured.

[0056] Reference: Principle of Measurement of Collagen ProductionAbility

[0057] Since proline is a main component of the amino acids that composecollagen, fibroblasts are cultured in a medium containing ³H-proline,and the ³H activity taken up into collagen in the cells is measured.Units are in d.p.m., and represent the number of daltons ofradioactivity released per minute.

[0058] Test Results:

[0059] As shown in FIG. 1, according to the results of a collagenproduction recovery test, the collagen production ability of fibroblastsdamaged by active oxygen was determined to be significantly improved byL-arginine and ethanolamine. Although L-arginine and ethanolamine arecontained in the product of Example 3, since the amounts are excessivelysmall, production was nearly equal to Example 1. When 1% L-arginine and1% ethanolamine were further added to the product of Example 3,production nearly completely recovered.

[0060] Namely, although remarkable recovery is observed with L-arginineor ethanolamine alone, if both L-arginine and ethanolamine are presentand their amounts are increased, the collagen production ability ofdamaged fibroblasts can be nearly completely restored to its originalnormal level.

TEST EXAMPLE 2

[0061] A moisture retention duration test was conducted.

[0062] Moisture retention refers to the peak of the amount of skinmoisture (skin electrical conductivity) 15 minutes after application,while moisture retention duration refers to the integral value of acurve indicated by the amount of skin moisture (skin electricalconductivity) from 30 minutes to 120 minutes after application.

[0063] Samples:

[0064] Example 4 (1% L-arginine simple preparation) L-arginine (NakaraiTesuku) 1.00 g 95% Ethanol 2.00 mL Parabene 0.18 g Purified soy beanlecithin 0.05 g

[0065] Make up a final amount of 100.00 g by addition of purified water.

[0066] Example 5 (1% Ethanolamine simple preparation) Ethanolamine(Nakarai Tesuku) 1.00 g 95% Ethanol 2.00 mL Parabene 0.18 g Purified soybean lecithin 0.05 g

[0067] Make up a final amount of 100.00 g by addition of purified water.

[0068] Example 6 (0.2% L-arginine+0.02% Ethanolamine+simple preparation)Example 3 90.00 mL 95% Ethanol 2.00 mL Parabene 0.18 g Purified soy beanlecithin 0.05 g

[0069] Make up a final amount of 100.00 g by addition of purified water.

[0070] Comparative Example 1 (simple preparation) 95% Ethanol 2.00 mLParabene 0.18 g Purified soy bean lecithin 0.05 g

[0071] Make up a final amount of 100.00 g by addition of purified water.

[0072] Comparative Example 2 (Hyaluronic acid+simple preparation) Sodiumhyaluronate (2) 1.00 g 95% Ethanol 2.00 mL Parabene 0.18 g Purified soybean lecithin 0.05 g

[0073] Make up a final amount of 100.00 g by addition of purified water.

[0074] Panelists: 5 healthy volunteers

[0075] Test Method: Each sample was applied to the side of the forearmof the panelists (4×4 cm²) followed by measurement of epidermal keratinmoisture content at 15, 30, 60, 90 and 120 minutes after application.

[0076] Keratin contains salts, amino acids and other electrolytes inaddition to moisture. Consequently, although current does not flowthrough pure water, since electrolytes are contained in keratin in theskin, current flows corresponding to the amount of moisture present ifmoisture is present. The parameter that is actually measured iselectrical conductivity, which is the inverse of the resistance thatcomposes impedance.

[0077] Measurement Method:

[0078] (1) The test site is washed with soap.

[0079] (2) The test site is exposed in a constant temperature andconstant humidity room at a temperature of 20° C. and humidity of 50%,and the skin is allowed to reach a steady state by allowing thepanelists to rest quietly starting 60 minutes before measurement.

[0080] (3) The moisture content of keratin at the test site is. measuredand used as the value before application.

[0081] (4) After uniformly applying 0.03 mL aliquots of sample to thetest site four times, the sample is gently wiped off with gauze.

[0082] (5) The moisture content of the keratin at the test site 15, 30,60, 90 and 120 minutes after application, and that of keratin at a siteat which sample is not applied as a control, were measured.

[0083] Numerical values obtained by subtracting the value beforeapplication and value of the site where sample was not applied from thekeratin moisture content for each measurement time were taken torepresent skin moisture content.

[0084] Test Apparatus:

[0085] SKICON-200 (IBS Epidermal Keratin Moisture Measuring System (3.5MHz high-frequency conductivity measuring system))

[0086] Test Results:

[0087] The results of the moisture retention duration test are as shownin FIGS. 2 and 3.

[0088] Although peak values rose even at 15 minutes after applicationand moisture retention effects were remarkable for Examples 4, 5 and 6,moisture retention continued beyond 30 minutes and lasted for 2 hours.Although continuation of moisture retention was observed with eitherL-arginine or ethanolamine alone, when both substances were present,moisture retention duration was enhanced more than when either substancewas used alone even at lower concentrations.

[0089] On the other hand, although peaks were observed after 15 minutesin the case of Comparative Examples 1 and 2, moisture content returnedto its original level after 30 minutes, and continuation of moistureretention was not observed at all.

TEST EXAMPLE 3

[0090] A moisture retention ability test was conducted as an indicatorof the state of skin health.

[0091] Samples:

[0092] Example 4 (L-arginine+simple preparation)

[0093] Example 5 (Ethanolamine+simple preparation)

[0094] Example 6 (L-arginine+ethanolamine+simple preparation)

[0095] Example 7 (L-arginine+ethanolamine+body soap preparation) Example3 20.00 mL Lauric acid 2.50 g Myristic acid 7.50 g Palmitic acid 2.50 gOleic acid 2.50 g Lauroyldiethanolamide 5.00 g Glycerin 20.00 g Parabene0.20 g Caustic potash 3.60 g Edetate 0.20 g Fragrance q.s.

[0096] Make up a final amount of 100.00 g by addition of purified water.

[0097] Comparative Example 1 (simple preparation)

[0098] Comparative Example 3 Lauric acid 2.50 g Myristic acid 7.50 gPalmitic acid 2.50 g Oleic acid 2.50 g Lauroyldiethanolamide 5.00 gGlycerin 20.00 g Parabene 0.20 g Caustic potash 3.60 g Edetate 0.20 gFragrance q.s.

[0099] Make up a final amount of 100.00 g by addition of purified water.

[0100] Subjects: 4 healthy volunteers

[0101] Measurement Method:

[0102] (1) The test site is washed with soap.

[0103] (2) The test site is exposed in a constant temperature andconstant humidity room at a temperature of 20° C. and humidity of 50%,and the skin is allowed to reach a steady state by allowing the subjectsto rest quietly starting 60 minutes before measurement.

[0104] (3) The moisture content of keratin at the test site is measured.

[0105] (4) 0.03 mL of distilled water is placed over the test site andwiped off with gauze 10 seconds later followed by measurement of keratinmoisture content at the test site immediately, 30, 60, 90 and 120seconds after wiping off.

[0106] (5) 0.03 mL aliquots of sample are applied to the test site threetimes and allowed to stand for 15 minutes.

[0107] (6) The test site is washed well.

[0108] (7) After 120 minutes, keratin moisture content is measured after120 seconds by performing the same procedure as in step (4).

[0109] Moisture retention ability is determined in the manner indicatedbelow.

Moisture retention ability (%)=[Keratin moisture content 30-120 secondsafter moisture loading/Keratin moisture content immediately aftermoisture loading]×100

[0110] It should be noted that, moisture retention ability (ratio) wasexpressed as the ratio obtained when the moisture retention abilitybefore washing (%) is given a value of 1.

[0111] Test Apparatus: Same as Test Example 2.

[0112] Test Results:

[0113] The results of the moisture retention ability test are as shownin FIGS. 4 and 5.

[0114] Although there was no increase whatsoever in moisture retentionability, which represents the health of the skin, observed forComparative Example 1, the moisture retention ability 2 hours afterapplication in Examples 4, 5 and 6 increased considerably as comparedwith the moisture retention ability before application. When themoisture retention ability before application is taken to have a valueof 1, although that of Examples 4and 5 is nearly two times greater, inExample 6, the moisture retention ability increased to nearly threetimes greater.

[0115] In the case of washing with the product of Comparative Example 3,although moisture retention ability decreases as compared with thatbefore washing, washing with Example 7 resulted in an increase inmoisture retention ability as compared with before washing.

TEST EXAMPLE 4

[0116] A moisture retention duration test was conducted on persons withchapped skin.

[0117] Samples:

[0118] Example 4 (L-arginine+simple preparation)

[0119] Example 5 (ethanolamine+simple preparation)

[0120] Example 6 (L-arginine+ethanolamine+simple p reparation)

[0121] Comparative Example 1

[0122] Comparative Example 2

[0123] Panelists: 6 volunteers with chapped skin

[0124] Test Method:

[0125] Each sample was applied to the side of the forearm of thepanelists (4×4 cm²) followed by measurement of epidermal keratinmoisture content at 15, 30, 60 and 120 minutes after application.

[0126] Measurement Method: Same as measurement method of Test Example 2.

[0127] Determination of Skin Moisture Content: Same as Test Example 2.

[0128] Test Apparatus: Same as Test Example 2.

[0129] Test Results:

[0130] As shown in FIGS. 6 and 7, although the peaks increased andmoisture retention effects were remarkable after 15 minutes for Examples4, 5 and 6, moisture retention continued beyond 30 minutes and lastedfor 2 hours. Although this continuation of moisture retention was alsoobserved in Examples 4 and 5, the duration of moisture retention waseven greater in Example 6 that contained both L-arginine andethanolamine.

[0131] In Comparative Example 2, although a peak was observed after 15minutes and moisture retention effects were observed, moisture contentreturned to its original level after 30 minutes., and continuation ofmoisture retention with respect to chapped skin was not observed at all.

TEST EXAMPLE 5

[0132] Chapped skin was induced artificially and a recovery test wasconducted to observe the effects against damaged skin (skin susceptibleto both external and internal irritation).

[0133] Samples:

[0134] Example 6 (L-arginine+ethanolamine+simple preparation)

[0135] Example 8 (L-arginine+ethanolamine+cream preparation) Example 340.00 mL 1,3-butyleneglycol 6.00 g Concentrated glycerin 6.00 gMethylpolysiloxane 6.00 g Stearic acid 3.00 g Cetanol 3.00 g Cetyl2-ethylhexanoate 6.00 g Squalene 6.00 g Sucrose fatty acid ester 3.00 gNatural vitamin E 0.30 g Sodium casein 1.50 g Disodium edetate 0.03 gParabene 0.30 g

[0136] Make up a final amount of 100.00 g by addition of purified water.

[0137] Comparative Example 1

[0138] Comparative Example 2

[0139] Comparative Example 4 (cream preparation) 1,3-butyleneglycol 6.00g Concentrated glycerin 6.00 g Methylpolysiloxane 6.00 g Stearic acid3.00 g Cetanol 3.00 g Cetyl 2-ethylhexanoate 6.00 g Squalene 6.00 gSucrose fatty acid ester 3.00 g Natural vitamin E 0.30 g Sodium casein1.50 g Disodium edetate 0.03 g Parabene 0.30 g

[0140] Make up a final amount of 100.00 g by addition of purified water.

[0141] Panelists: 4 healthy volunteers

[0142] Test Method: After inducing chapped skin by treating a healthysite of the skin for 30 minutes with 5% SDS, each sample was appliedtwice per day, and the instantaneous moisture retention ability beforeapplication and from 1 day to 2 weeks after application was measuredaccording to the same method as Test Example 3.

[0143] Chapped Skin Induction Method: A glass cylinder was placed on thetest site and fixed in position with tape. Next, 10 mL of 5% SDS (sodiumlauryl sulfate) was poured into the glass cylinder to perform chappedskin treatment for 30 minutes while stirring occasionally. Finally, theSDS was suctioned out of the glass cylinder and the glass cylinder wasremoved.

[0144] Test Apparatus: Same as Test Example 2.

[0145] Test Results:

[0146] According to the results of the chapped skin recovery test (FIG.8), only natural recovery of the skin was observed with the simplepreparation form, the typical moisture retention agent, hyaluronic acid,and a typical cream preparation not containing L-arginine orethanolamine, and chapped skin improvement effects were not observed. Onthe other hand, in the case of Examples 6 and 8, moisture retentionability increased significantly in comparison with the control group at3, 5 and 7 days after the start of application, and moisture retentionability was higher than the untreated site (healthy site) starting at 5days after the start of application.

[0147] In this manner, Examples 6 and 8 were clearly demonstrated torapidly restore damaged skin and improve the skin to healthy skin to agreater extent than the untreated site.

[0148] The present invention was proven to rapidly restore damaged skinin a short period of time, enable the skin to reach a state that ishealthier than its original state, and have effects that improve theskin to its healthiest state. On the basis of these findings, thepresent invention was proven to act on chapped skin itself and conditionit, be able to prevent skin diseases caused by chapped skin, anddemonstrate chapped skin therapeutic effects.

TEST EXAMPLE 6

[0149] A clinical test was conducted on dry eczema, xeroderma and facialdry eczema patients to observe the therapeutic effects on skin diseasesproduced by skin conditioning, and those effects were evaluated in termsof the severity score of itchiness, sclerosis, cornification, scaling,cracking, erythema, dryness and wrinkles, as well as overall improvement(usefulness) with respect to each disease.

[0150] Samples:

[0151] Example 9 (L-arginine+milky liquid preparation) L-arginine(Nakarai Tesuku) 0.10 g 1,3-butyleneglycol 10.00 g Concentrated glycerin1.00 g Stearic acid 0.50 g Myristic acid 0.50 g Bleached beeswax 0.50 gTri-2-ethylhexanoate glycerin 4.80 g Octyldodecylmyristic acid 2.00 gSqualene 1.00 g Sucrose fatty acid ester 0.60 g Xanthane rubber 0.10 gNatural vitamin E 0.10 g Sodium casein 0.30 g Citric acid q.s. Disodiumedetate 0.02 g Parabene 0.20 g

[0152] Make up a final amount of 100.00 g by addition of soft water.

[0153] Panelists: 3 patients with dry eczema

[0154] 2 patients with xeroderma

[0155] 2 patients with facial dry eczema

[0156] Test Sites:

[0157] Sites having symptoms suitable for evaluation and sites that canbe compared to the left or right or above or below (comparison withnon-application).

[0158] External Application Method: Simple application twice per day(morning and evening).

[0159] Application Period: 3 weeks

[0160] Evaluation Items:

[0161] Evaluation items consisted of:

[0162] (1) Itchiness

[0163] (2) Sclerosis/cornification

[0164] (3) Scaling

[0165] (4) Cracking

[0166] (5) Erythema

[0167] (6) Dryness

[0168] (7) Wrinkles

[0169] Evaluation Method:

[0170] The evaluation items were evaluated according to the followingfour levels of a severity score as determined by visual examination.

[0171] 3: Advanced symptoms

[0172] 2: Moderate symptoms

[0173] 1: Mild symptoms

[0174] 0: No symptoms or symptoms disappeared

[0175] In addition, overall improvement (usefulness) was evaluatedaccording to the following four levels:

[0176] Extremely useful

[0177] Useful

[0178] Somewhat useful

[0179] Not useful

[0180] Test Results:

[0181] The results for overall improvement (usefulness) are as shown inFIG. 9. When Example 9 product was used in patients with dry eczema,xeroderma and facial dry eczema, the results demonstrated overallimprovement of 100%, a high degree of usefulness was obtained, andExample 9 was recognized to be extremely useful against these diseases.

[0182]FIG. 10 shows the changes in severity scores for itchiness,sclerosis and cornification. FIG. 11. shows the changes in severityscores for scaling and cracking. FIG. 12 shows the changes in severityscores for erythema, dryness and wrinkles. All effects appeared rapidly,and all symptoms were alleviated considerably after 1 week of use.Favorable improvement effects were also observed after 1 week, andnearly all symptoms had either been alleviated or disappeared after 3weeks. It should be noted that, there were no adverse side effectsobserved at all, there were no cases of relapse after use wasdiscontinued, and the patients were completely healed.

[0183] In this manner, the present invention is able to improve symptomsobserved in skin diseases such as itchiness, sclerosis, cornification,scaling, cracking, erythema, dryness and wrinkles through conditioningof the skin.

TEST EXAMPLE 7

[0184] A clinical test was conducted on asteatosis, xeroderma, facialdry eczema and progressive volar keratoderma patients to observe thetherapeutic effects on skin diseases produced by skin conditioning, andthose effects were evaluated in terms of the severity score ofitchiness, sclerosis, cornification, scaling, cracking, erythema,dryness and wrinkles, as well as overall improvement (usefulness) withrespect to each disease.

[0185] Samples:

[0186] Example 10 (L-arginine+ethanolamine+milky liquid preparation)Example 3 35.00 mL 1,3-butyleneglycol 10.00 g Concentrated glycerin 1.00g Stearic acid 0.50 g Myristic acid 0.50 g Bleached beeswax 0.50 gTri-2-ethylhexanoate glycerin 4.80 g Octyldodecylmyristic acid 2.00 gSqualene 1.00 g Sucrose fatty acid ester 0.60 g Xanthane rubber 0.10 gNatural vitamin E 0.10 g Sodium casein 0.30 g Citric acid q.s. Disodiumedetate 0.02 g Parabene 0.20 g

[0187] Make up a final amount of 100.00 g by addition of soft water.Panelists: Asteatosis patients 6 Xeroderma patients 4 Facial dry eczemapatients 4 Progressive volar keratoderma 5 patients

[0188] Test Sites:

[0189] Sites having symptoms suitable for evaluation and sites that canbe compared to the left or right or above or below (comparison withnon-application).

[0190] External Application Method: Simple application once per day(morning and evening).

[0191] Application Period: 3 weeks

[0192] Evaluation Items:

[0193] Evaluation items consisted of:

[0194] (1) Itchiness

[0195] (2) Sclerosis/cornification

[0196] (3) Scaling

[0197] (4) Cracking

[0198] (5) Erythema

[0199] (6) Dryness

[0200] (7) Wrinkles

[0201] Evaluation Method:

[0202] The evaluation items were evaluated according to the followingfour levels of a severity score as determined by visual examination.

[0203] 3: Advanced symptoms

[0204] 2: Moderate symptoms

[0205] 1: Mild symptoms

[0206] 0: No symptoms or symptoms disappeared

[0207] In addition, overall improvement (usefulness) was evaluatedaccording to the following four levels:

[0208] Extremely useful

[0209] Useful

[0210] Somewhat useful

[0211] Not useful

[0212] Test Results:

[0213] Overall improvement (usefulness) was as shown in FIG. 13.

[0214] When Example 10 was used in asteatosis, xeroderma, facial dryeczema and progressive volar keratoderma patients, it demonstratedoverall improvement of 94.74%, a high degree of usefulness was obtained,and Example 10 was observed to be extremely useful against thesediseases.

[0215]FIG. 14 shows the changes in severity scores for itchiness,sclerosis and cornification, FIG. 15 shows the changes in severityscores for scaling and cracking, and FIG. 16 shows the changes inseverity scores for erythema, dryness and wrinkles. All effects appearedrapidly, and all symptoms were alleviated considerably after 1 week ofuse. Favorable improvement effects were also observed after 1 week, andnearly all symptoms had either been alleviated or disappeared after 3weeks. Furthermore, there were no adverse side effects observed at all,there were no cases of relapse after use was discontinued, and thepatients were completely healed.

[0216] In this manner, the present invention is able to improve symptomsobserved in skin diseases such as itchiness, sclerosis, cornification,scaling, cracking, erythema, dryness and wrinkles through conditioningof the skin.

TEST EXAMPLE 8

[0217] Guinea pigs were irradiated with ultraviolet light, a phlogogenicfactor, followed by histological examination of the degree ofinflammatory changes in epidermal tissue and dermal tissue to observethe preventive and therapeutic effects on inflammation andphotoinflammation.

[0218] Samples:

[0219] Example 6 (L-arginine+ethanolamine+simple preparation)

[0220] Comparative Example 1 (simple preparation)

[0221] Experimental Animals: Guinea pigs, 5

[0222] Test Site:

[0223] Shaved back of guinea pigs (comparison with simple preparation)

[0224] Test Method:

[0225] The backs of the experimental animals were shaved and hair wasremoved with a depilatory cream three days before irradiation withultraviolet light.

[0226] The test site was irradiated with ultraviolet light, andapplication of samples was started immediately after irradiation.

[0227] In order to make a histological evaluation of inflammation causedby irradiation with ultraviolet light, biopsies were performed with a 6mm disposable punch on days 7 and 14 after irradiation, the specimenswere immersed in 10% neutral formalin solution and fixed followed bypreparing tissue sections.

[0228] Application Method: Simple application twice a day afterirradiation (morning and evening)

[0229] Application Period: 2 weeks

[0230] Evaluation Method:

[0231] Using keratin hyperplasia and parakeratosis as indicators ofinflammatory changes of epidermal tissue, and cellular infiltration andvasodilation as indicators of inflammatory changes in dermal tissue, thetissue sections were observed and evaluations were made according to thefollowing five levels of a severity score (inflammation intensity).

[0232] Severity Score

[0233] 4: Advanced symptoms

[0234] 3: Moderate symptoms

[0235] 2: Mild symptoms

[0236] 1: Slight symptoms

[0237] 0: No symptoms or symptoms disappeared

[0238] Test Results:

[0239] The test results are as shown in FIGS. 17, 18, 19 and 20.

[0240] Example 6 of the present invention was clearly demonstrated tohave an effect that heals vasodilation in the early stage of theoccurrence of inflammation in dermal tissue, and was also observed tonot only have a therapeutic effect in the early stage, but also apreventive effect that prevents full-scale onset of inflammation. Inaddition, it was also clearly shown to rapidly heal cellularinfiltration, which is a symptom of inflammation in the dermis.Furthermore, keratin hyperplasia and parakeratosis, which areabnormalities in the epidermis accompanying inflammation, were alsoobserved to be alleviated.

[0241] On the basis of these findings, inflammation andphotoinflammation were clearly demonstrated to be prevented and healedby skin conditioning.

TEST EXAMPLE 9

[0242] A 2-hour moisture retention duration test was performed on atopicskin.

[0243] Panelists: 7 persons with atopic skin

[0244] Test Method: Same as Test Example 2 .

[0245] Measurement Method: Same as Text Example 2

[0246] Test Apparatus: Same as Test Example 2

[0247] The samples were as shown below.

[0248] Example 4 (1% L-arginine simple preparation) L-arginine (NakaraiTesuku) 1.00 g 95% Ethanol 2.00 mL Parabene 0.18 g Purified soy beanlecithin 0.05 g

[0249] Make up a final amount of 100.00 g by addition of purified water.

[0250] Example 5 (1% ethanolamine simple preparation) Ethanolamine(Nakarai Tesuku) 1.00 g 95% Ethanol 2.00 mL Parabene 0.18 g Purified soybean lecithin 0.05 g

[0251] Make up a final amount of 100.00 g by addition of purified water.

[0252] Example 6 (0.2% L-arginine +0.02% ethanolamine+simplepreparation) Example 3 90.00 mL 95% Ethanol 2.00 mL Parabene 0.18 gPurified soy bean lecithin 0.05 g

[0253] Make up a final amount of 100.00 g by addition of purified water.

[0254] Example 11 (1% 2-methoxyethylamine simple preparation)2-methoxyethylamine (Tokyo Kasei Kogyo) 1.00 g 95% Ethanol 2.00 mLParabene 0.18 g Purified soy bean lecithin 0.05 g

[0255] Make up a final amount of 100.00 g by addition of purified water.

[0256] Example 12 (1% O-Phosphorylethanolamine simple preparation)O-Phosphorylethanolamine (Tokyo Kasei Kogyo) 1.00 g 95% Ethanol 2.00 mLParabene 0.18 g Purified soy bean lecithin 0.05 g

[0257] Make up a final amount of 100.00 g by addition of purified water.

[0258] Example 13 (1% 2-Ethylaminoethanol simple preparation)2-Ethylaminoethanol (Tokyo Kasei Kogyo Co., Ltd) 1.00 g 95% Ethanol 2.00mL Parabene 0.18 g Purified soy bean lecithin 0.05 g

[0259] Make up a final amount of 100.00 g by addition of purified water.

[0260] Example 14 (1% Diethanolamine simple preparation) Diethanolamine(Mitsui Toatsu Chemicals) 1.00 g 95% Ethanol 2.00 mL Parabene 0.18 gPurified soy bean lecithin 0.05 g

[0261] Make up a final amount of 100.00 g by addition of purified water.

[0262] Example 15 (1% 2-Dimethylaminoethanol simple preparation)2-Dimethylaminoethanol (Kanto Kagaku) 1.00 g 95% Ethanol 2.00 mLParabene 0.18 g Purified soy bean lecithin 0.05 g

[0263] Make up a final amount of 100.00 g by addition of purified water.

[0264] Example 16 (1% Choline simple preparation) Choline (NakaraiTesuku) 1.00 g 95% Ethanol 2.00 mL Parabene 0.18 g Purified soy beanlecithin 0.05 g

[0265] Make up a final amount of 100.00 g by addition of purified water.

[0266] Example 17 (1% 2-Amino-hydroxymethyl-1,3-propanediol simplepreparation) 2-Amino-hydroxymethyl-1,3-propanediol 1.00 g (Kanto Kagaku)95% Ethanol 2.00 mL Parabene 0.18 g Purified soy bean lecithin 0.05 g

[0267] Make up a final amount of 100.00 g by addition of purified water.

[0268] Example 18 (1% Noradrenaline simple preparation) Noradrenaline(Nakarai Tesuku) 1.00 g 95% Ethanol 2.00 mL Parabene 0.18 g Purified soybean lecithin 0.05 g

[0269] Make up a final amount of 100.00 g by addition of purified water.

[0270] Example 19 (1% Phenethylamine simple preparation) Phenethylamine(Kanto Kagaku) 1.00 g 95% Ethanol 2.00 mL Parabene 0.18 g Purified soybean lecithin 0.05 g

[0271] Make up a final amount of 100.00 g by addition of purified water.

[0272] Example 20 (1% Ethylenediamine simple preparation)Ethylenediamine (Nakarai Tesuku) 1.00 g 95% Ethanol 2.00 mL Parabene0.18 g Purified soy bean lecithin 0.05 g

[0273] Make up a final amount of 100.00 g by addition of purified water.

[0274] Example 21 (1% Taurine simple preparation) Taurine (NakaraiTesuku) 1.00 g 95% Ethanol 2.00 mL Parabene 0.18 g Purified soy beanlecithin 0.05 g

[0275] Make up a final amount of 100.00 g by addition of purified water.

[0276] Example 22 (1% Phosphatidylethanolamine simple preparation)Phosphatidylethanolamine (Kanto Kagaku) 1.00 g 95% Ethanol 2.00 mLParabene 0.18 g Purified soy bean lecithin 0.05 g

[0277] Make up a final amount of 100.00 g by addition of purified water.

[0278] Example 23 (1% N-(2-Hydroxyethyl)acetamide simple Preparation)N-(2-Hydroxyethyl)acetamide 1.00 g (Kanto Kagaku) 95% Ethanol 2.00 mLParabene 0.18 g Purified soy bean lecithin 0.05 g

[0279] Make up a final amount of 100.00 g by addition of purified water.

[0280] Example 24 (1% 2-(Metylamino)ethanol simple preparation)2-(Metylamino)ethanol (Kanto Kagaku) 1.00 g 95% Ethanol 2.00 mL Parabene0.18 g Purified soy bean lecithin 0.05 g

[0281] Make up a final amount of 100.00 g by addition of purified water.

[0282] Example 25 (1% 2-Anilinoethanol simple preparation)2-Anilinoethanol (Kanto Kagaku) 1.00 g 95% Ethanol 2.00 mL Parabene 0.18g Purified soy bean lecithin 0.05 g

[0283] Make up a final amount of 100.00 g by addition of purified water.

[0284] Example 26 (1% 2-(Benzylamino)ethanol simple preparation)2-(Benzylamino)ethanol (Kanto Kagaku) 1.00 g 95% Ethanol 2.00 mLParabene 0.18 g Purified soy bean lecithin 0.05 g

[0285] Make up a final amount of 100.00 g by addition of purified water.

[0286] Example 27 (1% 3-Amino-1-propanol simple preparation)3-Amino-1-propanol (Kanto Kagaku) 1.00 g 95% Ethanol 2.00 mL Parabene0.18 g Purified soy bean lecithin 0.05 g

[0287] Make up a final amount of 100.00 g by addition of purified water.

[0288] Example 28 (1% 2-Amino-1-butanol simple preparation)2-Amino-1-butanol (Nakarai Tesuku) 1.00 g 95% Ethanol 2.00 mL Parabene0.18 g Purified soy bean lecithin 0.05 g

[0289] Make up a final amount of 100.00 g by addition of purified water.

[0290] Example 29 (1% Putrescine simple preparation) Putrescine (SigmaChemical) 1.00 g 95% Ethanol 2.00 mL Parabene 0.18 g Purified soy beanlecithin 0.05 g

[0291] Make up a final amount of 100.00 g by addition of purified water.

[0292] Example 30 (1% DL-Pyroglutamic acid simple preparation)DL-Pyroglutamic acid (Tokyo Kasei Kogyo) 1.00 g 95% Ethanol 2.00 mLParabene 0.18 g Purified soy bean lecithin 0.05 g

[0293] Make up a final amount of 100.00 g by addition of purified water.

[0294] Example 31 (1% Triethanolamine simple preparation)Triethanolamine (Mitsui Toatsu Chemicals) 1.00 g 95% Ethanol 2.00 mLParabene 0.18 g Purified soy bean lecithin 0.05 g

[0295] Make up a final amount of 100.00 g by addition of purified water.

[0296] Example 32 (Rice preparation containing 0.03% L-arginine)

[0297] 1 kg of unpolished rice was crushed with a crusher. After adding3000 mL of water, 7.5 g of α-amylase, 8 g of protease and 8 g ofpeptidase and heating to 55° C., the mixture was allowed to stand for 10hours while holding at that temperature. Next, the temperature wasgradually raised and extraction was performed by boiling for 5 minutes.After cooling to 20° C., the mixture was press-filtered and the pH ofthe filtrate was lowered to 3.3 by addition of citric acid. 8 g ofacidic protease and 8 g of acidic carboxypeptidase were added followedby allowing to react for 10 hours at 55° C.

[0298] Next, the mixture was heated to 70° C. and then filtered aftercooling to obtain 2700 mL of product containing 354 mg/L of L-arginine.

[0299] Example 33 (Rice preparation containing 0.03% L-arginine+simplepreparation) Example 32 (containing 90.00 mL 0.03% L-arginine from rice)95% Ethanol 2.00 mL Parabene 0.18 g Purified soy bean lecithin 0.05 g

[0300] Make up a final amount of 100.00 g by addition of purified water.

[0301] Example 34 (1% 2-Methoxyethylamine+rice preparation containing0.03% L-arginine+simple preparation) Example 32 (containing 0.03% 90.00mL L-arginine from rice) 2-Methoxyethylamine (Tokyo Kasei Kogyo) 0.90 g95% Ethanol 2.00 mL Parabene 0.18 g Purified soy bean lecithin 0.05 g

[0302] Make up a final amount of 100.00 g by addition of purified water.

[0303] Example 35 (1% O-Phosphorylethanolamine+rice preparationcontaining 0.03% L-arginine+simple preparation) Example 32 (containing90.00 mL 0.03% L-arginine from rice) O-Phosphorylethanolamine 0.90 g(Tokyo Kasei Kogyo) 95% Ethanol 2.00 mL Parabene 0.18 g Purified soybean lecithin 0.05 g

[0304] Make up a final amount of 100.00 g by addition of purified water.

[0305] Example 36 (1% 2-Ethylaminoethanol+rice preparation containing0.03% L-arginine+simple preparation) Example 32 (containing 0.03% 90.00mL L-arginine from rice) 2-Ethylaminoethanol (Tokyo Kasei Kogyo) 0.90 g95% Ethanol 2.00 mL Parabene 0.18 g Purified soy bean lecithin 0.05 g

[0306] Make up a final amount of 100.00 g by addition of purified water.

[0307] Example 37 (1% Diethanolamine+rice preparation containing 0.03%L-arginine+simple preparation) Example 32 (containing 0.03% 90.00 mLL-arginine from rice) Diethanolamine (Mitsui Toatsu Chemicals) 0.90 g95% Ethanol 2.00 mL Parabene 0.18 g Purified soy bean lecithin 0.05 g

[0308] Make up a final amount of 100.00 g by addition of purified water.

[0309] Example 38 (1% 2-Dimethylaminoethanol+rice preparation containing0.03% L-arginine+simple preparation) Example 32 (containing 0.03% 90.00mL L-arginine from rice) 2-Dimethylaminoethanol (Kanto Kagaku) 0.90 g95% Ethanol 2.00 mL Parabene 0.18 g Purified soy bean lecithin 0.05 g

[0310] Make up a final amount of 100.00 g by addition of purified water.

[0311] Example 39 (1% Choline+rice preparation containing 0.03%L-arginine +simple preparation) Example 32 (containing 90.00 mL 0.03%L-arginine from rice) Choline (Nakarai Tesuku) 0.90 g 95% Ethanol 2.00mL Parabene 0.18 g Purified soy bean lecithin 0.05 g

[0312] Make up a final amount of 100.00 g by addition of purified water.

[0313] Example 40 (1% 2-Amino-2-hydroxymethyl-1,3-propanediol+ricepreparation containing 0.03% L-arginine+simple preparation) Example 32(containing 0.03% 90.00 mL L-arginine from rice)2-Amino-2-hydroxymethyl-1,3-propanediol 0.90 g (Kanto Kagaku) 95%Ethanol 2.00 mL Parabene 0.18 g Purified soy bean lecithin 0.05 g

[0314] Make up a final amount of 100.00 g by addition of purified water.

[0315] Example 41 (1% Noradrenaline+rice preparation containing 0.03%L-arginine+simple preparation) Example 32 (containing 0.03% 90.00 mLL-arginine from rice) Noradrenaline (Nakarai Tesuku) 0.90 g 95% Ethanol2.00 mL Parabene 0.18 g Purified soy bean lecithin 0.05 g

[0316] Make up a final amount of 100.00 g by addition of purified water.

[0317] Example 42 (1% Phenethylamine+rice preparation containing 0.03%L-arginine+simple preparation) Example 32 (containing 0.03% 90.00 mLL-arginine from rice) Phenethylamine (Kanto Kagaku) 0.90 g 95% Ethanol2.00 mL Parabene 0.18 g Purified soy bean lecithin 0.05 g

[0318] Make up a final amount of 100.00 g by addition of purified water.

[0319] Example 43 (1% Ethylenediamine+rice preparation containing 0.03%L-arginine+Simple Preparation) Example 32 (containing 0.03% 90.00 mLL-arginine from rice) Ethylenediamine (Nakarai Tesuku) 0.90 g 95%Ethanol 2.00 mL Parabene 0.18 g Purified soy bean lecithin 0.05 g

[0320] Make up a final amount of 100.00 g by addition of purified water.

[0321] Example 44 (1% Taurine+rice preparation containing 0.03%L-arginine+simple preparation) Example 32 (containing 90.00 mL 0.03%L-arginine from rice) Taurine (Nakarai Tesuku) 0.90 g 95% Ethanol 2.00mL Parabene 0.18 g Purified soy bean lecithin 0.05 g

[0322] Make up a final amount of 100.00 g by addition of purified water.

[0323] Example 45 (1% Phosphatidylethanolamine+rice preparationcontaining 0.03% L-arginine+simple preparation) Example 32 (containing0.03% 90.00 mL L-arginine from rice) Phosphatidylethanolamine (KantoKagaku) 0.90 g 95% Ethanol 2.00 mL Parabene 0.18 g Purified soy beanlecithin 0.05 g

[0324] Make up a final amount of 100.00 g by addition of purified water.

[0325] Example 46 (1% N-(2-Hydroxyethyl)acetamide+rice preparationcontaining 0.03% L-arginine+simple preparation) Example 32 (containing0.03% 90.00 mL L-arginine from rice) N-(2-Hydroxyethyl) acetamide 0.90 g(Kanto Kagaku) 95% Ethanol 2.00 mL Parabene 0.18 g Purified soy beanlecithin 0.05 g

[0326] Make up a final amount of 100.00 g by addition of purified water.

[0327] Example 47 (1% 2-(Methylamino)ethanol+rice preparation containing0.03% L-arginine+simple preparation) Example 32 (containing 0.03% 90.00mL L-arginine from rice) 2-(Methylamino) ethanol (Kanto Kagaku) 0.90 g95% Ethanol 2.00 mL Parabene 0.18 g Purified soy bean lecithin 0.05 g

[0328] Make up a final amount of 100.00 g by addition of purified water.

[0329] Example 48 (1% 2-Anilinoethanol+rice preparation containing 0.03%L-arginine+simple preparation) Example 32 (containing 0.03% 90.00 mLL-arginine from rice) 2-Anilinoethanol (Kanto Kagaku)  0.90 g 95%Ethanol  2.00 mL Parabene  0.18 g Purified soy bean lecithin  0.05 g

[0330] Make up a final amount of 100.00 g by addition of purified water.

[0331] Example 49 (1% 2-(Benzylamino)ethanol+rice preparation containing0.03% L-arginine+simple preparation) Example 32 (containing 0.03% 90.00mL L-arginine from rice) 2-(Benzylamino)ethanol (Kanto Kagaku)  0.90 g95% Ethanol  2.00 mL Parabene  0.18 g Purified soy bean lecithin  0.05 g

[0332] Make up a final amount of 100.00 g by addition of purified water.

[0333] Example 50 (1% 3-Amino-1-propanol+rice preparation containing0.03% L-arginine+simple preparation) Example 32 (containing 0.03% 90.00mL L-arginine from rice) 3-Amino-1-propanol (Kanto Kagaku)  0.90 g 95%Ethanol  2.00 mL Parabene  0.18 g Purified soy bean lecithin  0.05 g

[0334] Make up a final amount of 100.00 g by addition of purified water.

[0335] Example 51 (1% 2-Amino-1-butanol+rice preparation containing0.03% L-arginine+simple preparation) Example 32 (containing 0.03% 90.00mL L-arginine from rice) 2-Amino-1-butanol  0.90 g (Nakarai Tesuku) 95%Ethanol  2.00 mL Parabene  0.18 g Purified soy bean lecithin  0.05 g

[0336] Make up a final amount of 100.00 g by addition of purified water.

[0337] Example 52 (1% Putrescine+rice preparation containing 0.03%L-arginine+simple preparation) Example 32 (containing 0.03% 90.00 mLL-arginine from rice) Putrescine (Sigma Chemical)  0.90 g 95% Ethanol 2.00 mL Parabene  0.18 g Purified soy bean lecithin  0.05 g

[0338] Make up a final amount of 100.00 g by addition of purified water.

[0339] Example 53 (1% DL-Pyroglutamine acid+rice preparation containing0.03% L-arginine+simple preparation) Example 32 (containing 0.03% 90.00mL L-arginine from rice) DL-Pyroglutamine acid (Tokyo Kasei Kogyo)  0.90g 95% Ethanol  2.00 mL Parabene  0.18 g Purified soy bean lecithin  0.05g

[0340] Make up a final amount of 100.00 g by addition of purified water.

[0341] Example 54 (1% Triethanolamine+rice preparation containing 0.03%L-arginine+Simple Preparation) Example 32 (containing 0.03% 90.00 mLL-arginine from rice) Triethanolamine (Mitsui Toatsu Chemicals)  0.90 g95% Ethanol  2.00 mL Parabene  0.18 g Purified soy bean lecithin  0.05 g

[0342] Make up a final amount of 100.00 g by addition of purified water.

[0343] Comparative Example 1 (simple preparation) 95% Ethanol 2.00 mLParabene 0.18 g Purified soy bean lecithin 0.05 g

[0344] Make up a final amount of 100.00 g by addition of purified water.

[0345] Comparative Example 2 (Hyaluronic acid+simple preparation) Sodiumhyaluronate 1.00 g 95% Ethanol 2.00 mL Parabene 0.18 g Purified soy beanlecithin 0.05 g

[0346] Make up a final amount of 100.00 g by addition of purified water.

[0347] The results of the moisture retention duration test are as shownin FIGS. 21 through 31. With respect to atopic skin, moisture retentioneffects were remarkable 15 minutes after application, and moistureretention continued beyond 30 minutes for 2 hours. Although continuationof moisture retention was observed with either L-arginine orethanolamine alone, when two kinds of substances were present, moistureretention duration was enhanced more than when either substance was usedalone even at lower concentrations (see Example 6 in FIG. 21).

[0348] Although Examples 34 through 54 (referred to as the “former”) aremixtures containing 0.03% L-arginine in Examples 11 through 31 (referredto as the “latter”), respectively, the former demonstrated highermoisture retention duration than the latter (see FIGS. 27 through 31).

TEST EXAMPLE 10

[0349] A moisture retention ability test was performed on atopic skin.

[0350] Panelists: 4 persons with atopic skin

[0351] Measurement Method: Same as measurement method of Test Example 3

[0352] Test Apparatus: Same as test apparatus of Test Example 2

[0353] The samples were as shown below.

[0354] Example 4 (1% L-arginine simple preparation)

[0355] Example 5 (1% Ethanolamine simple preparation)

[0356] Example 6 (0.2% L-arginine+0.02% ethanolamine+simple preparation)

[0357] Example 11 (1% 2-Methoxyethylamine+simple preparation)

[0358] Example 14 (1% Diethanolamine simple preparation)

[0359] Example 16 (1% Choline simple preparation)

[0360] Example 17 (1% 2-Amino-2-hydroxymethyl-1,3-propanediol simplepreparation)

[0361] Example 18 (1% Noradrenaline simple preparation)

[0362] Example 34 (2-Methoxyethylamine+rice preparation containing 0.03%L-arginine +simple preparation)

[0363] Example 37 (1% Diethanolamine+rice preparation containing 0.03%L-arginine+simple preparation)

[0364] Example 39 (1% Choline+rice preparation containing 0.03%L-arginine+simple preparation)

[0365] Example 40 (1% 2-Amino-2-hydroxymethyl-1,3-propanediol+ricepreparation containing 0.03% L-arginine+simple preparation)

[0366] Example 41 (1% Noradrenaline+rice preparation containing 0.03%L-arginine+simple preparation)

[0367] Comparative Example 1 (simple preparation)

[0368] The results of the moisture retention ability test are as shownin FIGS. 32 through 34.

[0369] Although effects that increased moisture retention ability foratopic skin were not observed at all for Comparative Example 1, themoisture retention ability 2 hours after applying the samples of theabove-mentioned Examples of the present invention increase significantlyas compared with before application.

[0370] In FIG. 32, although moisture retention ability increased witheither L-arginine alone (Example 4) or ethanolamine alone (Example 5),in the case both substances were present (Example 6), moisture retentionability was increased more than when either substance was used aloneeven at lower concentrations.

[0371] Although Examples 34 through 41 (referred to as the “former”) aremixtures of rice preparations containing 0.03% L-arginine with Examples11 through 18 (referred to as the “latter”), respectively, the formerdemonstrated higher moisture retention ability than the latter (FIG.34).

[0372] In this manner, the samples of the present invention increasedthe skin's barrier function by acting on the corneal layer, and acted onepidermal keratocytes not present in the corneal layer to produce acorneal layer having a high barrier function.

TEST EXAMPLE 11

[0373] The amount of moisture loss from the skin (transepidermalmoisture evaporation volume) was measured to confirm barrier functionimprovement effects.

[0374] Panelists: 4 persons with atopic skin

[0375] Test Method: Each sample was applied to the side of the forearmof the panelists (approx. 0.3×0.3 cm) followed by measurement oftransepidermal moisture evaporation volume at 60 and 120 minutes afterapplication.

[0376] Measurement Method:

[0377] (1) The test site is washed with soap.

[0378] (2) The test site is exposed in a constant temperature andconstant humidity room at a temperature of 20° C. and humidity of 50%,and the skin is allowed to reach a steady state by allowing thepanelists to rest quietly starting 60 minutes before measurement.

[0379] (3) Transepidermal water loss (TEWL) at the test site is measuredfor about 1 minute (the rate of moisture evaporation at the test site ismeasured as TEWL (g/m² h) automatically by software computation bycontacting a cylindrical probe of the TEWAMETER TM210 perpendicular tothe test site).

[0380] Test Apparatus:

[0381] TEWAMETER TM210 (Nippon Eurotech)

[0382] TEWAMETER Software Ver. 1.1 (Nippon Eurotech)

[0383] Samples: Same as the samples used in Test Example 10

[0384] The test results for transepidermal moisture evaporation volumeare as shown in FIGS. 35 through 37.

[0385] The amount of moisture loss is greater in atopic skin prior toapplication of the samples of the present invention as compared withhealthy skin due to a decrease in the skin's barrier function. Theamount of moisture loss was decreased nearly to the level of healthyskin following application of the samples of the present invention toatopic skin for 4 weeks, and the skin's barrier mechanism and functionwere determined to have been improved.

[0386] Although Examples 34 through 41 (referred to as the “former”) aremixtures of rice preparations containing 0.03% L-arginine with Examples11 through 18 (referred to as the “latter”), respectively, the formerdemonstrated greater effects that reduced the amount of moisture lossthan the latter (FIG. 37).

[0387] In this manner, impairment of the skin's barrier mechanism andfunction was improved, and internal moisture loss was inhibited byapplying the samples of the present invention to atopic skin.

TEST EXAMPLE 12

[0388] An allergic reaction inhibition test was conducted in housedust-sensitized model animals (guinea pigs).

[0389] Experimental Animals: Guinea pigs, 6

[0390] Test Method:

[0391] (1) House dust extract and adjuvant were mixed and injectedsubcutaneously into the guinea pigs to sensitize.

[0392] (2) After sensitization was established, the abdomens of theguinea pigs were shaved to produce chapped skin.

[0393] (3) The samples were applied to the site where chapped skin wasproduced.

[0394] (4) House dust extract was applied to the sample applicationsite.

[0395] (5) Skin reaction was evaluated for 1-5 days after step (4).

[0396] Evaluation of the induced skin reaction (dermatitis) was scoredbased on the following-standards.

[0397] 0: No reaction

[0398] 1: Mild erythema

[0399] 2: Moderate erythema

[0400] 3: Serious erythema

[0401] 4: Serious erythema accompanied by edema

[0402] The samples were as shown below

[0403] Example 55 (simple preparation containing 40% Example 3) Example32 (containing 0.2% 40.00 mL L-arginine and 0.02% ethanolamine fromrice) 95% Ethanol  2.00 mL Parabene  0.18 g Purified soy bean lecithin 0.05 g

[0404] Make up a total amount of 100.00 g by addition of purified water.

[0405] Comparative Example 1 (simple preparation)

[0406] The results of the allergic reaction inhibition test in housedust-sensitized model animals (guinea pigs) are shown in FIG. 38.

[0407] When a sample of the present invention was applied to housedust-sensitized guinea pig skin in which chapped skin had been producedartificially followed by reapplication of house dust, the degree ofhouse dust extract-induced dermatitis was inhibited over the course of 5days after application.

[0408] In this manner, skin in which impairment of the skin's barriermechanism and function was improved by application of a sample of thepresent invention was able to prevent infiltration of antigen from theoutside and inhibit dermatitis.

TEST EXAMPLE 13

[0409] A clinical test was conducted on atopic skin of patients withatopic dermatitis.

[0410] Panelists: 12 patients with atopic dermatitis

[0411] Test Sites:

[0412] The test sites consisted of sites having symptoms suitable forevaluation that enabled comparison of a site using Example 8 and a siteusing Comparative Example 5 either to the, left and right or above andbelow.

[0413] External Application Method:

[0414] Simple application at each site separately for Example 8 andComparative Example 5 twice per day (morning and evening).

[0415] Application Period: 4 weeks

[0416] Evaluation Items:

[0417] Evaluation items consisted of the main symptoms of atopic skin.

[0418] (1) Skin dryness

[0419] (2) Scaling

[0420] (3) Itchiness

[0421] Evaluation Method:

[0422] The results of the site where Example 8 was applied wereevaluated for the evaluation items according to the following fourlevels of a severity score as determined by visual examination.

[0423] 3: Advanced symptoms

[0424] 2: Moderate symptoms

[0425] 1: Mild symptoms

[0426] 0: No symptoms or symptoms disappeared

[0427] In addition, improvement (usefulness) of effects as compared withComparative Example 5 was evaluated each week according to the followingfour levels:

[0428] Extremely useful

[0429] Useful

[0430] Somewhat useful

[0431] Not useful

[0432] Finally, the usefulness of the present invention was evaluated interms of the overall usefulness throughout the usage period.

[0433] The samples were as shown below.

[0434] Example 8 (Example 3+cream preparation) Example 3 (containing0.2% L-arginine and 0.02%  40.00 mL ethanolamine from rice) Dipotassiumglycyrrhetinate 0.10 g 1,3-Butyleneglycol 6.00 g Concentrated glycerin6.00 g Methylpolysiloxane 6.00 g Stearic acid 3.00 g Cetanol 3.00 gCetyl 2-Ethylhexanoate 6.00 g Squalene 6.00 g Sucrose fatty acid ester3.00 g dl-α-Tocopherol acetate 0.30 g Sodium casein 1.50 g Disodiumedetate 0.03 g Parabene 0.30 g

[0435] Make up a final amount of 100.00 g by addition of purified water.

[0436] Comparative Example 5 (cream preparation) Dipotassiumglycyrrhetinate 0.10 g 1,3-Butyleneglycol 6.00 g Concentrated glycerin6.00 g Methylpolysiloxane 6.00 g Stearic acid 3.00 g Cetanol 3.00 gCetyl 2-ethylhexanoate 6.00 g Squalene 6.00 g Sucrose fatty acid ester3.00 g dl-α-Tocopherol acetate 0.30 g Sodium casein 1.50 g Disodiumedetate 0.03 g Parabene 0.30 g

[0437] Make up a final amount of 100.00 g by addition of purified water.

[0438] Test Results:

[0439] When a sample of the present invention and Comparative Example 5were respectively used on skin susceptible to the induction ofdermatitis (atopic skin) located near to the affected area of atopicdermatitis patients, in contrast to Comparative Example 5 beingcompletely ineffective, the present invention demonstrated a high degreeof usefulness.

[0440]FIGS. 39 through 42 show the changes in severity scores of skindryness, scaling and itchiness. According to these results, the presentinvention alleviated skin symptoms such as skin dryness, scaling anditchiness associated with atopic dermatitis, and was observed todemonstrate a high degree of usefulness against each of these symptoms.There were no adverse side effects observed and a high degree of safetywas observed.

[0441] Since the present invention has remarkable effects againstitchiness, the vicious circle of itchiness leading to scratching,scratching leading to increased itchiness, and further scratchingleading to exacerbation of atopic dermatitis can be terminated, therebymaking it possible to prevent the onset and exacerbation of atopicdermatitis. In addition, as a result of being freed from itchiness, thepresent invention also has effects on the mental state of atopicdermatitis patients.

[0442] In this manner, the present invention is able to improve skinsymptoms of skin dryness, scaling and itchiness observed in atopic skin,thereby being able to prevent the onset and exacerbation of atopicdermatitis, by restoring the skin's barrier mechanism and functionthrough. conditioning of the skin. TEST EXAMPLE 14

[0443] A clinical test was conducted on the affected skin of atopicdermatitis patients to observe the therapeutic effects on atopicdermatitis as a result of skin conditioning and restoration of theskin's barrier mechanism and function.

[0444] Panelists: 7 patients with atopic dermatitis

[0445] Samples: Sample as in the case of Test Example 13.

[0446] Example 8 (Example 3+cream preparation)

[0447] Comparative Example 5 (cream preparation)

[0448] Test Sites:

[0449] The test sites consisted of sites having symptoms suitable forevaluation that enabled comparison of a site using Example 8 and a siteusing Comparative Example 5 either to the left and right or above andbelow.

[0450] External Application Method:

[0451] Simple application at each site separately for Example 8 andComparative Example 5 twice per day (morning and evening).

[0452] Application Period: 4 weeks

[0453] Evaluation Items:

[0454] Evaluation items consisted of the following:

[0455] (1) Itchiness

[0456] (2) Dry marks

[0457] (3) Erythema

[0458] (4) Lichenification

[0459] Evaluation Method:

[0460] The results of the site where Example 8 was applied wereevaluated for the evaluation items according to the following fourlevels of a severity score as determined by visual examination.

[0461] 3: Advanced symptoms

[0462] 2: Moderate symptoms

[0463] 1: Mild symptoms

[0464] 0: No symptoms or symptoms disappeared

[0465] In addition, improvement (usefulness) of effects as compared withComparative Example 5 was evaluated each week according to the followingfour levels:

[0466] Extremely useful

[0467] Useful

[0468] Somewhat useful

[0469] Not useful

[0470] Finally, the usefulness of the present invention was evaluated interms of the overall usefulness throughout the usage period.

[0471] Test Results:

[0472] When a sample of the present invention and Comparative Example 5were respectively used on atopic dermatitis patients, in contrast toComparative Example 5 being completely ineffective, the presentinvention demonstrated a high degree of usefulness as shown in FIGS. 43through 46.

[0473]FIGS. 43 through 46 show the changes in severity scores ofitchiness, dry marks, erythema and lichenification at the site of use ofExample 8 of the present invention. According to these results, thepresent invention alleviated skin symptoms such as itchiness, dry marks,erythema and lichenification associated with atopic dermatitis, and wasobserved to demonstrate a high degree of usefulness against each ofthese symptoms. There were no adverse side effects, rebound phenomenawere not observed following discontinuation of use, and there were nocases of recurrence.

[0474] Since the present invention has remarkable effects againstitchiness, the vicious circle of itchiness leading to scratching andscratching leading to exacerbation of atopic dermatitis can beterminated, and it is possible to prevent the onset and exacerbation ofatopic dermatitis. In addition, as a result of being freed fromitchiness, the present invention also has effects on the mental state ofatopic dermatitis patients.

[0475] In this manner, the present invention is able to improve skinsymptoms of itchiness, dry marks, erythema and lichenification observedin atopic dermatitis, thereby being able to heal this disease, throughconditioning of the skin.

TEST EXAMPLE 15

[0476] A clinical test was conducted on the affected skin of atopicdermatitis patients to observe the therapeutic effects on atopicdermatitis as a result of skin conditioning and restoration of theskin's barrier mechanism and function.

[0477] Panelists: 5 patients with atopic dermatitis

[0478] Samples:

[0479] Example 56 (1% Ethanolamine+cream preparation) Ethanolamine(Nakarai Tesuku) 1.00 g Dipotassium glycyrrhetinate 0.10 g1,3-Butyleneglycol 6.00 g Concentrated glycerin 6.00 gMethylpolysiloxane 6.00 g Stearic acid 3.00 g Cetanol 3.00 g Cetyl2-ethylhexanoate 6.00 g Squalene 6.00 g Sucrose fatty acid ester 3.00 gdl-α-Tocopherol acetate 0.30 g Sodium casein 1.50 g Disodium edetate0.03 g Parabene 0.30 g

[0480] Make up a final amount of 100.00 g by addition of purified water.

[0481] Comparative Example 5 (cream preparation)

[0482] Test Sites:

[0483] The test sites consisted of sites having symptoms suitable forevaluation that enabled comparison of a site using Example 56 and a siteusing Comparative Example 5 either to the left and right or above andbelow.

[0484] External Application Method:

[0485] Simple application at each site separately for Example 56 andComparative Example 5 twice per day (morning and evening).

[0486] Application Period: 4 weeks

[0487] Evaluation Items: Same as Test Example 13.

[0488] Evaluation Method: Same as Test Example 13.

[0489] Test Results:

[0490] When Example 56 of the present invention and Comparative Example5 were respectively used on atopic dermatitis patients, in contrast toComparative Example 5 being completely ineffective, Example 56 of thepresent invention demonstrated a high degree of usefulness as shown inFIGS. 47 through 50.

[0491]FIGS. 47 through 50 show the changes in severity scores ofitchiness, dry marks, erythema and lichenification at the site of use ofExample 56 of the present invention. According to these results, Example56 of the present invention alleviated skin symptoms such as itchiness,dry marks, erythema and lichenification associated with atopicdermatitis, and was observed to demonstrate a high degree of usefulnessagainst each of these symptoms. There were no adverse side effects,rebound phenomena were not observed following discontinuation of use,and there were no cases of recurrence.

[0492] Since the present invention has remarkable effects againstitchiness, the vicious circle of itchiness leading to scratching andscratching leading to exacerbation of atopic dermatitis can beterminated, and it is possible to prevent the onset and exacerbation ofatopic dermatitis. In addition, as a result of being freed fromitchiness, the present invention also has effects on the mental state ofatopic dermatitis patients.

[0493] In this manner, the present invention is able to improve skinsymptoms of itchiness, dry marks, erythema and lichenification observedin atopic dermatitis, thereby being able to heal this disease, throughconditioning of the skin.

[0494] The moisture retention agent used in the present inventioncontains one or more kinds of substances selected from the groupconsisting of polyvalent alcohols represented by glycerin,dipropyleneglycol and 1,3-butyleneglycol; sugars represented bysorbitol, maltitol, dextrin, hyaluronic acid and chitosan;mucopolysaccharides and sugar derivatives; polypeptides represented byelastin and collagen; organic acids and their salts represented bypyrrolidone carboxylic acid, citric acid and lactic acid;biopharmaceutical and natural moisture retention agents represented byrefined rice wine, rice bran, aloe, glycyrrhizac radix and chamomile;bio-component moisture retention agents represented by vitamins,placental extract, urea, lecithins, phospholipids, ceramides,cholesterols and sphingolipids; and, vegetable extracts, fruit extracts,kelp extracts, enzymes and inorganic salts; and, is one or moresubstances selected from the group consisting of animal oils, vegetableoils, hydrocarbons, higher alcohols and esters.

[0495] Drugs that can be used in pharmaceuticals, quasi-drugs andcosmetics which are externally applied skin preparations as claimed inthe present invention are one or more kinds of substances selected fromthe group consisting of bactericidal drugs, wound protective agents,wound healing agents, drugs for suppurative diseases, analgesic,anti-itching, astringent and antiphlogistic agents, immunosuppresants,drugs for parasitic skin diseases, skin softeners, hair agents, vitaminagents and biopharmaceuticals, while the bases are one or more kinds ofsubstances selected from the group consisting of moisture retentionagents, astringents, refrigerants, antioxidants, ultraviolet absorbers,infrared dispersants, preservatives, antibiotics, chelating agents,surfactants, foaming agents, stabilizers, penetrants, assistants, pHadjusters, buffers, emulsifiers, opacefiers, fragrances and pigments.

[0496] The dry skin symptoms which are targets of the present inventionare symptoms selected from atopic skin, dry or rough skin, aged skin,ichthyosis, dry skin, chapped skin, asteatosis, xeroderma, dry eczema,facial dry eczema and progressive volar keratoderma, and/or selectedfrom erythema, sclerosis and cornification, cracking, scaling, wrinkles,itching and dry marks, while skin aging symptoms are selected fromwrinkles and decreased skin tightness and elasticity, skin damage causedby ultraviolet rays is selected from spots and freckles, skin disordersarising from the epidermis are selected from turnover abnormalities,fineness and moistness, physicochemical skin disorders are selected fromcuts, burns and floor burns, biological skin disorders are selected fromathlete's foot and skin infections, while dermatitis and eczema areinflammatory cornification disorders (psoriasis).

[0497] The present invention demonstrates remarkable effectiveness inthe prevention and treatment of skin diseases such as atopic dermatitis,dry skin symptoms, pruritis, frostbite, cracking, chapped skin, skinaging symptoms, skin damage caused by ultraviolet rays, darkening,blackening, skin disorders arising in the epidermis, physicochemicalskin disorders, skin symptoms caused by the use of water, soap,detergents, surfactants or solvents, adverse side effects of externallyapplied skin preparations, biological skin disorders, dermatitis, eczemaand other skin diseases.

[0498] Industrial Applicability

[0499] The present invention relates to a skin conditioner comprisingthe compound represented by the general formula:

[0500] (wherein, the symbols are the same as those defined in the text).Examples of active ingredients of the present invention includeL-arginine and ethanolamine. These active ingredients can be acquired aschemical synthesis products, or they may also be acquired in the form ofnatural substances. Preferable Examples of natural substances includesubstances containing L-arginine and/or ethanolamine obtained from rice.The skin conditioner as claimed in the present invention demonstratesremarkable effectiveness as an agent for the prevention and treatment ofatopic dermatitis and as a skin moisture retention agent.

1. A method of improving moisture retention ability of skin and/ortreating or protecting skin for another purpose, comprising applying toskin a composition comprising a compound selected from the groupconsisting of ethanolamine, 2-methoxyethylamine,o-phosphorylethanolamine, 2-ethylaminoethanol, diethanolamine,2-dimethylaminoethanol, choline,2-amino-2-hydroxymethyl-1,3-propanediol, noradrenalin, phenethylamine,ethylenediamine, taurine, phosphatidylethanolamine,N-(2-hydroxyethyl)acetoamide, 2-(methylamino)ethanol, 2-anilinoethanol,2-(benzylamino)ethanol, 3-amino-1-propanol, 2-amino-1-butanol,putrescine, DL-pyroglutamic acid and triethanolamine.
 2. The methodaccording to claim 1, wherein the composition further comprisesL-arginine.
 3. The method according to claim 2, wherein the compoundand/or L-arginine originate in a rice preparation.
 4. The methodaccording to claim 2, wherein the compound originates in a ricepreparation.
 5. The method according to claim 1, wherein the compositionfurther comprises a rice preparation in admixture with the compound. 6.The method according to claim 2, wherein the composition furthercomprises L-arginine and/or a rice preparation in admixture with thecompound.
 7. The method according to any one of claims 3-6, wherein therice preparation is produced by hydrating rice or crushed rice, addingamylase or protease and allowing to react, and adding yeast followingcompletion of the reaction to perform saccharification and fermentation.8. The method according to any one of claims 3-6, wherein the ricepreparation is produced by hydrating rice or crushed rice, adding one,two or all of amylase, protease and lipase, heating, and extracting byheating or repeating these reactions at least once.
 9. The methodaccording to claim 1, wherein the compound originates in an animal,plant or microbial preparation.
 10. The method according to claim 2,wherein the compound and/or L-arginine originate in an animal, plant ormicrobial preparation.
 11. The method according to claim 1, wherein thecomposition further comprises an animal, plant or microbial preparationin admixture with the compound.
 12. The method according to claim 2,wherein the composition further comprises L-arginine and/or an animal,plant or microbial preparation in admixture with the compound.
 13. Themethod according to any one of claims 9-12, wherein the animal, plant ormicrobial preparation is produced by fermenting an animal, plant ormicrobial substance, or adding a fermenting sugar, followed byfermentation.
 14. The method according to any one of claims 9-12,wherein the animal, plant or microbial preparation is produced by addingwater, as necessary, to the animal, plant or microbial material, addingone, two or all of amylase, protease and lipase, heating, and extractingby heating or further repeating these reactions at least once.
 15. Themethod according to claim 1, wherein the skin to which the compositionis applied requires prevention, prevention of exacerbation or treatmentof atopic dermatitis.
 16. The method according to claim 1, wherein theskin to which the composition is applied requires moisturization. 17.The method according to claim 1, wherein the skin to which thecomposition is applied requires restoration of the barrier mechanism andfunction thereof.
 18. The method according to claim 1, wherein the skinto which the composition is applied requires conditioning of corneallayer thereof.
 19. The method according to claim 1, wherein the skin towhich the composition is applied requires conditioning of epidermalkeratocytes thereof.
 20. The method according to claim 1, wherein theskin to which the composition is applied requires conditioning epidermisthereof.
 21. The method according to claim 1, wherein the compound isapplied to the skin in the form of a combination of the compound and amoisture retention agent.
 22. The method according to claim 21, whereinthe moisture retention agent comprises one or more substances selectedfrom the group consisting of polyvalent alcohols selected from the groupconsisting of glycerin, dipropyleneglycol and 1,3-butyleneglycol; sugarsselected from the group consisting of sorbitol, maltitol, dextrin,hyaluronic acid and chitosan; mucopolysaccharides and sugar derivatives;alcohols selected from the group consisting of glycerin,dipropyleneglycol and 1,3-butyleneglycol; sugars selected from the groupconsisting of sorbitol, maltitol, dextrin, hyaluronic acid and chitosan;mucopolysaccharides and sugar derivatives; polypeptides selected fromthe group consisting of elastin and collagen; organic acids and theirsalts selected from the group consisting of pyrrolidone carboxylic acid,citric acid, lactic acid and salts thereof; biopharmaceutical andnatural moisture retention agents selected from the group consisting ofrefined rice wine, rice bran, aloe, licorice and chamomile;bio-component moisture retention agents selected from the groupconsisting of vitamins, placental extract, urea, lecithins,phospholipids, ceramides, cholesterols and sphingolipids; and vegetableextracts, fruit extracts, kelp extracts, enzymes and inorganic salts;and further comprises one or more substances selected from the groupconsisting of animal oils, vegetable oils, hydrocarbons, higher alcoholsand esters.
 23. The method according to claim 1, wherein the compositionfurther comprises a drug and/or base that can be used in externallyapplied skin preparations as pharmaceuticals, quasi-drugs and cosmetics.24. The method according to claim 23, wherein the drug comprises one ormore kinds of substances selected from the group consisting ofbactericidal drugs, wound protective agents, wound healing agents, drugsfor suppurative diseases, analgesic, anti-itching, astringent andantiphlogistic agents, immunosuppresants, drugs for parasitic skindiseases, skin softeners, hair agents, vitamin agents andbiopharmaceuticals, and the base comprises one or more kinds ofsubstances selected from the group consisting of moisture retentionagents, astringents, refrigerants, antioxidants, ultraviolet absorbers,infrared dispersants, preservatives, antibiotics, chelating agents,surfactants, foaming agents, stabilizers, penetrants, assistants, pHadjusters, buffers, emulsifiers, opacifiers, fragrances and pigments.25. The method according to claim 1, wherein the skin to which thecomposition is applied requires prevention or treatment of skin diseaseselected from the group consisting of atopic dermatitis, dry skinsymptoms, pruritis, frostbite, cracking, chapped skin, skin agingsymptoms, skin damage caused by ultraviolet rays, darkening, blackening,skin disorders arising in the epidermis, physicochemical skin disorders,skin symptoms caused by the use of water, soap, detergents, surfactantsor solvents, adverse side effects of externally applied skinpreparations, biological skin disorders, dermatitis and eczema.
 26. Themethod according to claim 25, wherein dry skin symptoms are symptomsselected from atopic skin, dry or rough skin, aged skin, ichthyosis, dryskin, chapped skin, asteatosis, xeroderma, dry eczema, facial dry eczemaand progressive volar keratoderma, and/or selected from erythema,sclerosis and cornification, cracking, scaling, wrinkles, itching anddry marks, while skin aging symptoms are selected from wrinkles anddecreased skin tightness and elasticity, skin damage caused byultraviolet rays is selected from spots and freckles, skin disordersarising from the epidermis are selected from turnover abnormalities,fineness and moistness, physicochemical skin disorders are selected fromcuts, burns and floor burns, biological skin disorders are selected fromathlete's foot and skin infections, and inflammatory cornificationdisorders are selected from the group consisting to dermatitis andeczema.
 27. The method according to claim 25, wherein the skin diseaseis skin aging symptoms.
 28. The method according to claim 25, whereinthe skin disease is selected from the group consisting of darkening,wrinkles and decreased skin tightness and elasticity, and spots.
 29. Themethod according to claim 1, wherein the composition comprises cosmetic,quasi-drug or pharmaceutical.